Studies on the receptors and signal transduction mechanisms of angiotensin II (AII) and ACTH were performed in adrenal glomerulosa cells and Xenopus Laevis oocytes. A novel AII receptor subtype was cloned from the zona glomerulosa of the rat adrenal gland, and was shown to be coupled to calcium mobilization in oocytes and transfected COS cell. This receptor subtype (AT1B or AT3) is preferentially expressed in the adrenal and pituitary glands, and may mediate selective actions of AII in these tissues. The mas oncogene, which has been proposed to encode an AII receptor, was found to increase the responsiveness of pre- existing AII receptor in oocytes and transfected cells, but this is not itself an AII receptor. In Xenopus oocytes, the finding that activation of AII receptors on follicular cells sends a signal through gap junctions to elevate cytoplasmic calcium within the oocyte was extended to identify the nature of the intracellular communication process. The AII-regulated process of signal transfer was found to operate through an Ins(1,4,5)P3-dependent mechanism rather than through transfer of calcium into the oocyte and subsequent calcium-induced calcium release. The roles of Ins(1,4,5)P3 and Ins(1,3,45)P4 in calcium signaling were analyzed in fibroblasts transfected with rat brain Ins(1,4,5)P3 3- kinase. In such cells, the marked over-production of Ins(12,3,4,5)P4 was associated with a decrease in Ins(1,4,5)P3 levels and commensurate attenuation of the cytoplasmic calcium signal. The reduction in Ins(1,4,5)P3 formation and calcium signaling in 3-kinase transfected cells was similar during activation of both G-protein coupled receptors and growth factor receptors. These findings support the role of Ins(1,4,5)P3 as the major determinant of agonist-induced calcium signaling, and indicate that Ins(1,3,4,5)P4 does not contribute significantly to this process. The distribution of the previously defined AT1 and AT2 subtypes of the AII receptor in the rat brain revealed that AT2 receptors were much more abundant in immature animals, and that AT1 receptors were localized in areas related to the regulation of blood pressure, fluid intake, and pituitary hormone secretion. The abundance and differential localization of AT2 receptors in young animals, and the age-related changes in relative expression of the receptor subtypes, suggests that AII exerts specific actions according to the developmental stage of the central nervous system. The adrenal receptor for ACTH was expressed in Xenopus oocytes and shown to be coupled through Gs to activation of adenylate cyclase. The extracellular cAMP response to ACTH is a sensitive index of receptor expression in oocytes, and was utilized to demonstrate that the adrenal ACTH receptor is encoded by a 1.1-2.0 kb mRNA that can be functionally identified in frog oocytes.